Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Corporate & Special Sales
    • Journal Claims
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Permissions
    • Advertisers
    • Continuing Education
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI

User menu

  • Subscribe
  • My alerts
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
Journal of Nuclear Medicine
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI
  • Subscribe
  • My alerts
  • Log in
  • Log out
  • My Cart
Journal of Nuclear Medicine

Advanced Search

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Corporate & Special Sales
    • Journal Claims
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Permissions
    • Advertisers
    • Continuing Education
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • Follow JNM on Twitter
  • Visit JNM on Facebook
  • Join JNM on LinkedIn
  • Subscribe to our RSS feeds
OtherBASIC SCIENCE INVESTIGATIONS

99mTc-N-NOET Imaging for Myocardial Perfusion: Can It Offer More Than We Already Have?

Daniel Fagret, Catherine Ghezzi and Gérald Vanzetto
Journal of Nuclear Medicine September 2001, 42 (9) 1395-1396;
Daniel Fagret
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Catherine Ghezzi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gérald Vanzetto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • PDF
Loading

A neutral, lipophilic 99mTc-labeled compound proposed as a myocardial perfusion imaging agent is 99mTc-(N-ethoxy-N-ethyl-dithiocarbamato)ni-trido (N-NOET) (1). 99mTc-N-NOET has a high myocardial uptake in humans, with 3% of the injected dose in the heart 5 min after injection (2), a high first-pass extraction fraction in canine models (3) and in isolated rabbit hearts (4), and a myocardial uptake that correlates with myocardial blood flow (3,5) over a wide range of flow, with a plateau in 99mTc-N-NOET uptake only at very high flow rates (>4 mL . min−1 . g−1 in a canine model), as observed with 201Tl (5). 99mTc-N-NOET exhibits significant redistribution in dog models (3,6) and in human clinical studies (7). Finally, safety and dosimetry are comparable with that of the other technetium tracers (2).

Characteristics that 99mTc-N-NOET has in common with 201Tl include a high first-pass extraction fraction, a good correlation with coronary blood flow, and a redistribution phenomenon. However, 99mTc-N-NOET has a more favorable dosimetry, and mechanisms of redistribution (6) and myocardial uptake (8) are different. In addition, 99mTc-N-NOET uptake does not reflect myocardial cellular viability but, rather, coronary blood flow, at least in an experimental model of acutely infarcted, reperfused myocardium (9).

Compared with currently used technetium complexes (sestamibi and tetrofosmin), 99mTc-N-NOET has a better myocardial uptake (3% of injected dose vs. 1.2% and 1.5% of injected dose for technetium complexes) and a higher pulmonary uptake (20% of injected dose at rest vs. 1.7% and 2.6%) (2,10,11). As far as the heart/lung uptake ratio is concerned, that of 99mTc-N-NOET is always lower than that of other technetium complexes (2). The correlation of technetium complexes’ uptake with coronary blood flow shows a plateau at 2–2.5 times the basal flow values for sestamibi and tetrofosmin (12,13), whereas this plateau is reached at 3–3.5 times the basal flow values for 99mTc-N-NOET and 201Tl (5). In contrast to sestamibi and tetrofosmin, 99mTc-N-NOET undergoes a redistribution phenomenon that can be used in clinical practice. Finally, safety and dosimetry are comparable for all 3 technetium complexes (2). Known characteristics of 99mTc-N-NOET are much closer to those of 201Tl than to other technetium complexes; nevertheless, 99mTc-N-NOET is definitely not a technetium analog of 201Tl.

99mTc-N-NOET allows imaging of myocardial perfusion abnormalities for very weak variations of coronary flow because of the good correlation of its cardiac uptake with high coronary flow rates. The study by Takehana et al. (14) presented in this issue of The Journal of Nuclear Medicine is consistent with this observation. Thus, residual critical stenosis can be determined more accurately with 99mTc-N-NOET than with sestamibi (14). This possibility of revealing weak reductions of coronary flow reserve might become useful when perfusion scintigraphy is expected to accurately identify patients with coronary flow reserve abnormalities attributed with coronary atherosclerosis who should benefit from treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Indeed, in current practice, heterogeneity of 201Tl uptake under stress, without any segmentary abnormality, is often observed. In these patients, dyslipidemia, noninsulin-dependent diabetes, or even high blood pressure is always found. A diminution of coronary flow reserve has been reported in such patients even in the absence of significant coronary artery stenosis (15–17), and these alterations of endothelial function can be revealed by either PET (15,17) or SPECT imaging (18–20). Furthermore, we now know that coronary endothelial dysfunction predicts long-term cardiovascular event rates (21), but we also know that aggressive cholesterol-lowering therapy with HMG-CoA reductase inhibitors for a period of 2–6 mo improves myocardial perfusion in these patients (22,23).

Heterogeneity of perfusion tracer uptake could be an additional semiological criterion, together with the extent and the severity of the segmentary perfusion defects. In this context, 99mTc-N-NOET, like 201Tl, could become a valuable tool for evaluating this heterogeneity. Therefore, the finalization of mathematic models would be required to quantify these heterogeneity patterns.

Clinical confirmation of the redistribution phenomenon of 99mTc-N-NOET in a large population of patients will allow the same exploration as 201Tl stress redistribution but with a more favorable dosimetry. The results of the ongoing clinical trials with 99mTc-N-NOET will, in the near future, tell us whether these expectations are confirmed.

Three aspects of the biologic behavior of 99mTc-N-NOET require further investigation:

  • The heart/lung uptake ratio of 99mTc-N-NOET is lower than that of other technetium tracers or even of 201Tl, although, in our experience, the 99mTc-N-NOET heart/ lung uptake ratio correlates with that of 201Tl. However, this ratio is sufficient to obtain good quality images in most patients (2,7). In some cases, pulmonary uptake is detectable, notably at rest. Is this relative pulmonary hyperfixation associated with an increase in pulmonary activity or with a reduction of cardiac activity? Why does it only occur in certain patients? What is its pathophysiologic meaning?

  • The cellular uptake mechanisms of 99mTc-N-NOET have not yet been elucidated. In cultured newborn rat cardiomyocytes, 99mTc-N-NOET has been shown to bind to cellular membranes, with a particularly high affinity to L-type calcium channels, in a nonenergy-dependent manner (8). In contrast, studies on isolated perfused rat hearts (24) and in vivo rat hearts (25) suggest that 99mTc-N-NOET might preferably bind to the endothelium.

  • Is 99mTc-N-NOET a tracer of myocardial tissue viability? In a canine experimental model of reperfused acute myocardial infarction, myocardial uptake of 99mTc-N-NOET reflects the magnitude of flow restoration but not myocardial cellular viability, as does 201Tl (9). In this experiment, however, blood flow was normal at the time of 99mTc-N-NOET injection. As we know, the restoration of normal blood flow allows long-term improvement of myocardial function (stunned myocardium, i.e., myocardial viability in clinical practice). Therefore, we can hypothesize that 99mTc-N-NOET, a pure tracer of myocardial blood flow, might be a good predictor of clinical viability. However, this point needs to be investigated further.

In summary, 99mTc-N-NOET is a new tracer of myocardial perfusion. Although it presents, like 201Tl, a redistribution phenomenon, it is not a technetium analog of 201Tl. Moreover, 99mTc-N-NOET is not equivalent to either sestamibi or tetrofosmin. Perfectly controlled experimental studies, such as those presented by Takehana et al. (14), will allow a better understanding of 99mTc-N-NOET behavior and therefore more precisely define the place it will take among the currently available cardiac perfusion tracers.

Footnotes

  • Received Mar. 23, 2001; revision accepted Apr. 12, 2001.

    For correspondence or reprints contact: Daniel Fagret, MD, PhD, Laboratoire d’Etudes de Radiopharmaceutiques, Faculté de Médecine, Université de Grenoble, INSERM EMI 0008-CEA LRC 10, 38700 La Tronche, France.

REFERENCES

  1. ↵
    Pasqualini R, Duatti A, Bellande E, et al. Bis(dithiocarbamato)nitrido technetium-99m radiopharmaceuticals: a class of neutral myocardial imaging agents. J Nucl Med 1994;35:334–341.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    Vanzetto G, Fagret D, Pasqualini R, Mathieu JP, Chossat F, Machecourt J. Biodistribution, dosimetry and safety of myocardial perfusion imaging agent technetium 99mTcN-NOET in healthy volunteers. J Nucl Med. 2000;41:141–148.
    OpenUrlAbstract/FREE Full Text
  3. ↵
    Ghezzi C, Fagret D, Arvieux C, et al. Myocardial kinetics of TcN-NOET: a neutral lipophilic complex tracer of regional blood flow. J Nucl Med. 1995;36:1069–1077.
    OpenUrlAbstract/FREE Full Text
  4. ↵
    Holly TA, Leppo JA, Gilmore MP, Reinhard CP, Dahlbert S. The effect of ischemic injury on the cardiac transport of Tc-99m N-NOET in the isolated rabbit heart. J Nucl Cardiol. 1999;6:633–640.
    OpenUrlPubMed
  5. ↵
    Calnon DA, Ruiz M., Vanzetto G, Watson DD, Beller GA, Glover DK. Myocardial uptake of 99mTc-N-NOET and (201)Tl during dobutamine infusion: comparison with adenosine stress. Circulation. 1999;100:1653–1659.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    Vanzetto G, Calnon DA, Ruiz M, et al. Myocardial uptake and redistribution of 99mTc-N-NOET in dogs with either sustained coronary low flow or transient coronary occlusion: comparison to thallium-201 and myocardial blood flow. Circulation. 1997;96:2325–2331.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    Fagret D, Marie PY, Brunotte F, et al. Myocardial perfusion imaging with technetium 99m NOET: comparison with thallium 201 and coronary angiography. J Nucl Med. 1995;36:936–943.
    OpenUrlAbstract/FREE Full Text
  8. ↵
    Riou L, Ghezzi C, Mouton O, et al. Cellular uptake kinetics of 99mTcN-NOET in cardiomyocytes from newborn rats: calcium channel interaction. Circulation. 1998;98:2591–2597.
    OpenUrlAbstract/FREE Full Text
  9. ↵
    Vanzetto G, Glover DK, Ruiz M, et al. 99mTc-N-NOET myocardial uptake reflects myocardial blood flow and not viability in dogs with reperfused acute myocardial infarction. Circulation. 2000;101.: 2424–2430.
  10. ↵
    Wackers FJT, Berman DS, Maddahi J, et al. Technetium-99m hexakis 2-methoxy-isobutyl isonitrile: human biodistribution, dosimetry, safety and preliminary comparison to thallium-201 for myocardial perfusion imaging. J Nucl Med. 1989;30:301–311.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    Higley B, Smith FW, Smith T, et al. Technetium 99m 1,2bis[bis(2-ethoxyethyl)phosphino]ethane: human biodistribution and safety of a new myocardial perfusion imaging agent. J Nucl Med. 1993;34:30–38.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    Glover DK, Ruiz M, Edwards NC, et al. Comparison between 201Tl and 99mTc sestamibi uptake during adenosine-induced vasodilation as a function of coronary stenosis severity. Circulation. 1995;91:813–820.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    Glover DK, Ruiz M, Yang JY, Smith WH, Watson DD, Beller GA. Myocardial 99mTc-tetrofosmin uptake during adenosine-induced vasodilatation with either a critical or mild coronary stenosis. Circulation. 1997;96:2332–2338.
    OpenUrlAbstract/FREE Full Text
  14. ↵
    Takehana K, Beller GA, Ruiz M, Petruzella FD, Watson DD, Glover DK. Assessment of residual coronary stenosis using 99mTc-N-NOET vasodilator stress imaging to evaluate coronary flow reserve early after coronary reperfusion in a canine model of subendocardial infarction. J Nucl Med 2001;42:1388–1394.
    OpenUrlAbstract/FREE Full Text
  15. ↵
    Yokoyama I, Monomura SI, Ohtake T, et al. Improvement of impaired myocardial vasodilatation due to diffuse coronary atherosclerosis in hypercholesterolemics after lipid-lowering therapy. Circulation. 1999;100:117–122.
    OpenUrlAbstract/FREE Full Text
  16. Balletshofer BM, Ritting K, Enderle MD, et al. Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance. Circulation. 2000;101:1780–1784.
    OpenUrlAbstract/FREE Full Text
  17. ↵
    Lorenzoni R, Gistri R, Cecchi F, et al. Coronary vasodilator reserve is impaired in patients with hypertrophic cardiomyopathy and left ventricular dysfunction. Am Heart J. 1998;136:972–981.
    OpenUrlCrossRefPubMed
  18. ↵
    Verna E, Ceriani L, Giovanella L, Binaghi G, Garancini S. “False positive” myocardial perfusion scintigraphy findings in patients with angiographically normal coronary arteries: insights from intravascular sonography studies. J Nucl Med. 2000;41:1935–1940.
    OpenUrlAbstract/FREE Full Text
  19. Iriarte M, Caso R, Murga N, et al. Microvascular angina pectoris in hypertensive patients with left ventricular hypertrophy and diagnostic value of exercise thallium-201 scintigraphy. Am J Cardiol. 1995;75:335–339.
    OpenUrlCrossRefPubMed
  20. ↵
    Hasdai D, Gibbons RJ, Holmes DR, Higano ST, Lerman A. Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects. Circulation. 1997;96:3390–3395.
    OpenUrlAbstract/FREE Full Text
  21. ↵
    Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000;101:1899–1906.
    OpenUrlAbstract/FREE Full Text
  22. ↵
    Baller D, Notohamiprodjo G, Gleichmann U, Holzinger J, Weise R, Lehmann J. Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis. Circulation. 1999;99:2871–2875.
    OpenUrlAbstract/FREE Full Text
  23. ↵
    Eischstadt H, Eskotter H, Hoffmann I, Amthauer HW, Weidinger G. Improvement of myocardial perfusion by short-term fluvastatin therapy in coronary artery disease. Am J Cardiol. 1995;76:122A–125A.
    OpenUrlCrossRefPubMed
  24. ↵
    Johnson GJ, Allton IL, Nguyen KN, et al. Clearance of 99mTcN-NOET in normal, ischemic-reperfused and membrane-disrupted rat myocardium. J Nucl Cardiol. 1996;3:42–54.
    OpenUrlCrossRefPubMed
  25. ↵
    Uccelli L, Giganti M, Duatti A, et al. Subcellular distribution of technetium-99m-TcN-NOET in rat myocardium. J Nucl Med 1995;36:2075–2079.
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top

In this issue

Journal of Nuclear Medicine
Vol. 42, Issue 9
September 1, 2001
  • Table of Contents
  • Index by author
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Journal of Nuclear Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
99mTc-N-NOET Imaging for Myocardial Perfusion: Can It Offer More Than We Already Have?
(Your Name) has sent you a message from Journal of Nuclear Medicine
(Your Name) thought you would like to see the Journal of Nuclear Medicine web site.
Citation Tools
99mTc-N-NOET Imaging for Myocardial Perfusion: Can It Offer More Than We Already Have?
Daniel Fagret, Catherine Ghezzi, Gérald Vanzetto
Journal of Nuclear Medicine Sep 2001, 42 (9) 1395-1396;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
99mTc-N-NOET Imaging for Myocardial Perfusion: Can It Offer More Than We Already Have?
Daniel Fagret, Catherine Ghezzi, Gérald Vanzetto
Journal of Nuclear Medicine Sep 2001, 42 (9) 1395-1396;
Twitter logo Facebook logo LinkedIn logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
    • Footnotes
    • REFERENCES
  • Info & Metrics
  • PDF

Related Articles

  • Assessment of Residual Coronary Stenoses Using 99mTc-N-NOET Vasodilator Stress Imaging to Evaluate Coronary Flow Reserve Early After Coronary Reperfusion in a Canine Model of Subendocardial Infarction
  • PubMed
  • Google Scholar

Cited By...

  • 99mTc-N-DBODC5, a New Myocardial Perfusion Imaging Agent with Rapid Liver Clearance: Comparison with 99mTc-Sestamibi and 99mTc-Tetrofosmin in Rats
  • Synthesis and Biologic Evaluation of Monocationic Asymmetric 99mTc-Nitride Heterocomplexes Showing High Heart Uptake and Improved Imaging Properties
  • Google Scholar

More in this TOC Section

  • Counting Rate Characteristics and Image Distortion in Preclinical PET Imaging During Radiopharmaceutical Therapy
  • Design and Fabrication of Kidney Phantoms for Internal Radiation Dosimetry Using 3D Printing Technology
  • Synthesis and Biologic Evaluation of Novel 18F-Labeled Probes Targeting Prostate-Specific Membrane Antigen for PET of Prostate Cancer
Show more Invited Commentary

Similar Articles

SNMMI

© 2023 Journal of Nuclear Medicine

Powered by HighWire